The present invention relates to the use of rotating, levitating magnetic elements for mixing or pumping fluids or the like and, more particularly, to a system that is capable of pumping or mixing a temperature sensitive fluid using a rotating magnetic element or bearing that levitates above a cold superconducting element.
Most pharmaceutical solutions and suspensions manufactured on an industrial scale require highly controlled, thorough mixing to achieve a satisfactory yield and a uniform distribution of ingredients in the final product. Agitator tanks are frequently used to complete the mixing process, but a better degree of mixing is normally accomplished by using a mechanical stirrer or impeller (e.g., a set of mixing blades attached to a steel rod). Typically, the mechanical stirrer or impeller is simply lowered into the fluid through an opening in the top of the vessel and rotated by an external motor to create the desired mixing action.
One significant limitation or shortcoming of such an arrangement is the danger of contamination or leakage during mixing. The rod carrying the mixing blades or impeller is typically introduced into the vessel through a dynamic seal or bearing. This opening provides an opportunity for bacteria or other contaminants to enter, which of course can lead to the degradation of the product. A corresponding danger of environmental contamination exists in applications involving hazardous or toxic fluids, or suspensions of pathogenic organisms, since dynamic seals or bearings are prone to leakage. Cleanup and sterilization are also made difficult by the dynamic bearings or seals, since these structures typically include folds and crevices that are difficult to reach. Since these problems are faced by all manufacturers of sterile solutions, pharmaceuticals, or the like, the U.S. Food and Drug Administration (FDA) has consequently promulgated strict processing requirements for such fluids, and especially those slated for intravenous use.
Recently, there has also been an extraordinary increase in the use of biosynthetic pathways in the production of pharmaceutical materials, but problems plague those involved in this rapidly advancing industry. The primary problem is that suspensions of genetically altered bacterial cells frequently used to produce protein pharmaceuticals (insulin is a well-known example) require gentle mixing to circulate nutrients. If overly vigorous mixing or contact between the impeller and the vessel wall occurs, the resultant forces and shear stresses may damage or destroy a significant fraction of the cells, as well as protein molecules that are sensitive to shear stresses. This not only reduces the beneficial yield of the process, but also creates deleterious debris in the fluid suspension that requires further processing to remove.
In an effort to overcome this problem, others have proposed alternative mixing technologies. The most common proposal for stirring fluids under sterile conditions is to use a rotating, permanent magnet bar covered by an inert layer of TEFLON, glass, or the like. The magnetic bar is placed on the bottom of the agitator vessel and rotated by a driving magnet positioned externally to the vessel. Of course, the use of such an externally driven magnetic bar avoids the need for a dynamic bearing, seal or other opening in the vessel to transfer the rotational force from the driving magnet to the stirring magnet. Therefore, a completely enclosed system is provided. This of course prevents leakage and the potential for contamination created by hazardous materials (e.g., cytotoxic agents, solvents with low flash points, blood products, etc.), eases clean up, and allows for the desirable sterile interior environment to be maintained.
However, several well-recognized drawbacks are associated with this mixing technology, making it unacceptable for use in many applications. For example, the driving magnet produces not only torque on the stirring magnetic bar, but also an attractive axial thrust force tending to drive the bar into contact with the bottom wall of the vessel. This of course generates substantial friction at the interface between the bar and the bottom wall of the vessel. This uncontrolled friction generates unwanted heat and may also introduce an undesirable shear stress in the fluid. Consequently, fragile biological molecules, such as proteins and living cells that are highly sensitive to temperature and shear stress, are easily damaged during the mixing process, and the resultant debris may contaminate the product. Moreover, the magnetic bar stirrer does not generate the level of circulation provided by an impeller, and thus cannot be scaled up to provide effective mixing throughout the entire volume of large agitation tanks of the type preferred in commercial production operations.
In yet another effort to eliminate the need for dynamic bearings or shaft seals, some have proposed mixing vessels having external magnets that remotely couple the mixing impeller to a motor located externally to the vessel. A typical magnetic coupler consists of a drive magnet attached to the motor and a stirring magnet carrying an impeller. Similar to the magnetic bar technology described above, the driver and stirrer magnets are kept in close proximity to ensure that the coupling between the two is strong enough to provide sufficient torque. An example of one such proposal is found in U.S. Pat. No. 5,470,152 to Rains.
As described above, the high torque generated can drive the impeller into the walls of the vessel creating significant friction. By strategically positioning roller bearings inside the vessel, the effects of friction between the impeller and the vessel wall can be substantially reduced. Of course, high stresses at the interfaces between the ball bearings and the vessel wall or impeller assembly result in a grinding of the mixing proteins and living cells, and loss of yield. Further, the bearings are frequently sensitive to corrosive reactions with water-based solutions and other media and will eventually deteriorate, resulting in frictional losses which slow the impeller and reduce the mixing action and eventually also lead to undesirable contamination of the product. Bearings also add to the cleanup problems.
In an effort to address and overcome the limitations described above, still others have proposed levitated bearings designed to reduce the deleterious effects of friction resulting from magnetically coupled mixers. By using a specially configured magnetic coupler to maintain only a repulsive levitation force in the vertical direction, the large thrust force between the stirring and driving magnets can be eliminated, along with the resultant shear stress and frictional heating. An example of one such arrangement is shown in U.S. Pat. No. 5,478,149 to Quigg.
However, one limitation remaining from this approach is that only magnet-magnet interactions provide the levitation. This leads to intrinsically unstable systems that produce the desired levitation in the vertical direction, but are unable to control side-to-side movement. As a result, external contact bearings in the form of bearing rings are necessary to laterally stabilize the impeller. Although this xe2x80x9cpartialxe2x80x9d levitation reduces the friction between the impeller and the vessel walls, it does not totally eliminate the drawbacks of the magnetically coupled, roller bearing mixers previously mentioned.
In an effort to eliminate the need for contact or other types of mechanical roller bearings, complex feedback control has been proposed to stabilize the impeller. Typical arrangements use electromagnets positioned alongside the levitating magnet. However, the high power level required to attain only sub-millimeter separations between the levitating magnet and the stabilizing magnets constitutes a major disadvantage of this approach. Furthermore, this solution is quite complex, since the stabilizing magnets must be actively monitored and precisely controlled by complex computer-implemented software routines to achieve even a moderate degree of stability. As a consequence of this complexity and the associated maintenance expense, this ostensible solution has not been accepted in the commercial arena, and it is doubtful that it can be successfully scaled up for use in mixing industrial or commercial scale process volumes.
Still others have proposed the use of superconductive materials to levitate magnetic bearings. However, a significant limitation on the application of this technology to mixing systems results from the very cold temperatures required to create the desired superconductive effects. Even recently discovered xe2x80x9chigh temperaturexe2x80x9d superconductors often require temperatures on the order of 77 to 130 Kelvin to induce reliable, stable levitation in a magnetic bearing. In the past, the relatively wide separation distance required between the bearing, the cryostat outer wall, and the superconducting element to prevent unwanted cooling the fluid has limited the industrial applicability of this approach. To date, applications of this technology to fluids have been primarily in the pumping of cryogens or the like, such as those typically used in cold fusion experiments, in flywheels or other energy storage devices, or for space travel (see representative U.S. Pat. No. 5,747,426 to Abboud or U.S. Pat. No. 4,365,942 to Schmidt), where there is of course little concern for the inevitable cooling effect created.
In my prior U.S. Pat. No. 5,567,672, I describe a levitating magnetic xe2x80x9cnon-contactxe2x80x9d bearing that is thermally separated from the superconducting element by the double-walled vacuum jacket of the cryostat used to cool the superconducting element. This thermal separation reduces the thermal transfer between the cold superconducting element and the levitating bearing as well as the fluid being mixed, so that it could possibly be used in mixing relatively temperature sensitive fluids, such as cell suspensions or blood. However, the resultant increased separation distance between the superconducting element and the bearing created by the double wall vacuum gap significantly decreases the stability and the load capacity of the bearing. This limits the applications in which this arrangement is useful, and especially precludes use with particularly viscous fluids or with the large volumes of fluid typically present in commercial scale operations.
Thus, a need is identified for an improved system having a levitating magnetic bearing for mixing or pumping fluids, and especially ultra-pure, hazardous, or delicate fluid solutions or suspensions. The system would preferably employ a magnetic bearing that carries an impeller and levitates in a stable fashion to avoid contact with the bottom or side walls of the vessel. Since the bearing would levitate in the fluid, no mixing rod or other structure penetrating the mixing vessel would be necessary, thus eliminating the need for dynamic bearings or seals and all potentially deleterious effects associated therewith. Since penetration is unnecessary, the vessel could be completely sealed prior to mixing to avoid the potential for contamination and reduce the potential for exposure in the case of hazardous or biological fluids, such as contaminated blood or the like. The vessel and magnetic bearing could also be made of disposable materials and discarded after each use, which would eliminate the need for cleaning or sterilization. The absence of a mixing or stirring rod penetrating through the vessel would also allow a slowly rotating impeller to be held at an off-axis position in a sealed vessel, thus making it possible to independently rotate the vessel about its central axis to achieve very gentle, yet thorough, mixing.
The use of superconductivity to provide the desired levitation would be possible by thermally isolating and separating the superconducting element from the magnetic bearing and providing a separate, substantially isolated cooling source. This combined thermal isolation and separation would avoid creating any significant cooling in the vessel, magnetic bearing or the fluid being mixed or pumped. Overall, the proposed system would have superior characteristics over existing mixing or pumping technologies in sterility, mixing quality, safety and reliability, and would be readily adaptable for use in larger, industrial scale operations.
Accordingly, keeping the above needs in focus, a primary object of the present invention is to provide a system for pumping or mixing a fluid using a levitating magnetic bearing that overcomes the shortcomings, limitations and disadvantages of the previously described prior art approaches.
Another object of the present invention is to provide a pumping or mixing system wherein a magnetic bearing is levitated in the fluid in a stable fashion by a superconducting element, thereby eliminating the need for dynamic seals or bearings in the vessel walls and the frictional heat and shear stress created through the use of magnetic bar stirrers or the like.
A related object of the present invention to provide a fluid pumping or mixing system wherein the superconducting element is thermally isolated from the levitating magnetic bearing, thereby allowing it to be placed in relatively close proximity to the vessel while avoiding the creation of any significant cooling in the fluid held therein.
A further object is to provide a mixing system wherein the vessel containing the levitating magnetic bearing can be completely sealed prior to mixing.
Yet another object of the invention is to provide a fluid pumping or mixing system wherein the rotating, levitating magnetic bearing is selectively movable to an off-axis position within a sealed vessel.
Yet a further object is to provide a vessel and levitating magnetic bearing that are both fabricated of disposable materials and can simply be discarded after mixing or pumping is completed to avoid the need for clean up and sterilization.
Additional objects, advantages and other novel features of the invention will be set forth in part in the description that follows and in part will become apparent to those skilled in the art upon examination of the following or may be learned with the practice of the invention. The objects and advantages of the invention may be realized and obtained by means of the instrumentalities and combinations particularly pointed out in the appended claims.
To achieve the foregoing and other objects, and in accordance with the purposes of the present invention as described herein, a system that is capable of pumping or mixing temperature sensitive fluids using a magnetic pumping or mixing element, also referred to herein as a pumping or mixing structure or a bearing, levitated by a cold superconducting element is disclosed. The magnetic element/bearing, carries at least one impeller and is placed in a fluid vessel positioned externally to the outer wall of a cryostat or other housing for the superconducting element. A separate cooling source thermally linked to the superconducting element provides the necessary cooling to create the desired superconductive effects and induce levitation in the magnetic element, or bearing. In the preferred embodiment, the cryostat outer wall or other housing defines a chamber around the superconducting element that thermally isolates it from the vessel containing the magnetic element or bearing and the superconducting element. To minimize thermal transfer from the superconducting element contained in the chamber to the outer wall of housing, this chamber is evacuated or filled with an insulating material. This thermal isolation and separation means that the superconducting element can be placed in close proximity to the outer wall of the cryostat or other housing adjacent to the vessel to achieve a significant reduction in the separation distance between the levitating magnetic element, or bearing, and the superconducting element. This advantageously enhances the magnetic stiffness and loading capacity of the magnetic element/bearing as it levitates. However, since the superconducting element is thermally isolated from the wall or housing, the magnetic element/bearing, and hence the vessel and fluid contained therein, are not exposed to the cold temperatures required to generate the desired superconductive effects. By using means external to the vessel to rotate and stabilize the magnetic element/bearing levitating in the fluid, the desired pumping or mixing action is provided.
As should be appreciated from reviewing the foregoing description, several advantages are provided through the use of the mixing or pumping system of the present invention. Since the rotating magnetic bearing levitates in the fluid, there is no mechanical stirrer or mixing rod extending through any wall of the vessel, which means that the vessel can be completely sealed from the outside environment, if desired. This eliminates the need for a dynamic bearing or seal and the concomitant problems with leakage, sterility, and the like, which makes the present arrangement particularly well suited for use in pumping or mixing ultra-pure or hazardous fluids. Furthermore, exceptionally stable levitation is provided by the minimal separation distance between the superconducting element and the magnetic bearing, which is of course possible due to the thermal isolation and separation of the superconducting element from the outer wall of the cryostat. Contact-free, stable levitation reduces the incidence of frictional heating or unwanted shear stresses, both of which can have a significant deleterious effect on sensitive fluids, such as cell suspensions or the like.
In a preferred embodiment, the magnetic bearing includes first and second spaced permanent magnets mounted at the opposite ends of a support shaft that carries at least one impeller. The first magnet is placed in the fluid vessel closest to the outer wall of the cryostat such that it is levitated by the superconducting element. While those of skill in the art will understand that the polarity of the first permanent magnet is not critical for producing the desired levitation, it is preferred that it is disc-shaped and polarized in the vertical direction. This ensures that the magnetic field generated is substantially symmetrical and the desired stable levitation and free rotation relative to the vertical axis results.
The second permanent magnet is provided to form a magnetic coupling with the motive device for rotating the magnetic bearing, which is preferably a drive magnet rotated by a motor. In applications where the stability of the magnetic bearing is particularly important, the drive magnet includes more than one magnet, and in the most preferred embodiment has at least two sub-magnets that correspond to opposite polarity sub-magnets forming a part of the second permanent magnet. In addition to creating the desired magnetic coupling for transmitting the driving torque, these cooperating sub-magnets create an attractive force that balances with the levitational force produced by the superconducting element to keep the bearing properly balanced in the vertical direction. The cooperating sub-magnet pairs also keep the levitating bearing axially aligned and prevent side-to-side movement. In combination, the magnetic couplings created by the sub-magnet pairs allow the bearing to rotate in an exceptionally stable fashion. This reduces the chance of inadvertent contact between the bottom and side walls of the vessel, and eliminates the need for electromagnets, roller bearings, or like structures found in prior art pumps or mixers.
The superconducting element is preferably formed of melt-textured Yttrium-Barium Copper Oxide (YBCO), which is a well-known high temperature xe2x80x9ctype IIxe2x80x9d superconducting material, formed into a relatively thin pellet. The thermal link between the superconducting element and the cooling source is an elongate rod formed of a material having desirable thermal transfer characteristics. Metals, such as copper, brass, aluminum, or the like, are particularly well-suited for this purpose, but the use of any other material having good thermal conductance/low thermal resistance is possible. Preferably, the rod is cylindrical in shape such that one end has a relatively large surface area that fully contacts and engages an entire face of the superconducting element to maximize thermal transfer. While one end of the rod supports the superconducting element in the vacuum chamber defined by the outer wall of the cryostat or other housing, which remains at room temperature, the opposite end is kept in thermal contact with the cooling source. The cooling source may take the form of a separate cooling chamber in the cryostat holding a cryogen at a temperature between 4.2 and 130 Kelvin, and most preferably liquid nitrogen at a temperature between approximately 65-80 Kelvin. Instead of liquid cryogens, the use of alternate means for cooling the rod is possible, such as providing a separate closed cycle refrigerator is kept entirely outside of the cryostat or other housing for the superconducting element.
Since the magnetic bearing levitates without the need for a mixing rod or other form of driving shaft, it should be appreciated that the vessel containing the fluid may be completely sealed from the outside environment and used to mix, rather than pump, the fluid. By using such an arrangement, the potential for leakage or contamination during mixing is eliminated, as is the risk of human exposure to hazardous or biologically active fluids. Forming the sealed vessel and the magnetic bearing from disposable materials is also possible, such that they can simply be discarded after mixing is complete and the fluid is recovered, if necessary. This advantageously avoids the need for clean up or sterilization of the vessel and bearing.
Also, since there is no need for a dynamic bearing or seal for any drive shaft penetrating through a wall of the vessel, the vertical center axis of rotation of the magnetic bearing can be easily offset from the vertical center axis of the vessel. The vessel can then be rotated in a direction counterclockwise to the rotation of the bearing mounted in such an offset position. By doing so, gentle, yet thorough mixing may be provided in an efficient manner.
It should also be appreciated that other alternatives to a sealed vessel are also possible. Of course, the vessel may simply be open to the ambient environment, as may be desired during the mixing of some solutions or suspensions that require exposure to open air during mixing to achieve a desired result. Alternatively, the vessel may be substantially sealed with only an inlet and an outlet, such that the rotating impeller provides pumping action to move the fluid through the vessel. Manufacturing the open top or substantially sealed vessel of disposable materials is also possible, such that both the vessel and magnetic bearing can simply be discarded after use to avoid the need for clean up or sterilization.
A method of pumping or mixing a fluid in a vessel is also disclosed. The method includes the steps of placing a magnetic bearing carrying at least one impeller in the vessel. Levitation is induced in the magnetic bearing by a superconducting element positioned in a evacuated or insulated chamber defined by the outer wall of a cryostat or other housing. The chamber serves to thermally isolate and separate the vessel, fluid, and magnetic bearing from the superconducting element, which is thermally linked to a separate cooling source. Upon rotating the levitating magnetic bearing in the vessel, the desired mixing or pumping action is provided. As described above, the magnetic bearing and vessel may also be formed of disposable materials and discarded once mixing is complete and the fluid is recovered.
Still other objects of the present invention will become apparent to those skilled in this art from the following description wherein there is shown and described a preferred embodiment of this invention, simply by way of illustration of one of the modes best suited to carry out the invention. As it will be realized, the invention is capable of other different embodiments and its several details are capable of modification in various, obvious aspects all without departing from the invention. Accordingly, the drawings and descriptions will be regarded as illustrative in nature and not as restrictive.